HB-300, a novel arenavirus-based cancer immunotherapy in patients with metastatic castration-resistant prostate cancer.
Authors: David D. Chism, Biren Saraiya, Tanya B. Dorff, Brendan D. Curti, Edwin Melencio Posadas, Carlyle St. Paul, Subhendu Mukhopadhyay, Leena Desai, Henning Lauterbach, Rounak Nassirpour, Alexander Grill, Ali Manouchehri, Kia Katchar, Kevin Hibbert, Katia Schlienger, Susan F. Slovin
Journal: Journal of Clinical Oncology (2023)

TPS5108 Background: Prostate cancer is the most frequent type of malignant neoplasia in men. Immunotherapy targeting self-antigens in prostate cancer is evolving and requires overcoming multiple mechanisms that mediate immune tolerance. Sipuleucel-T, a cell-based therapy recognizing prostatic acid phosphatase (PAP) protein, is approved for treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) and induced PAP-specific T cell responses correlating with overall survival (OS). Poxvirus vectors encoding prostate-specific antigen (PSA) increased PSA-specific T cell levels and were associated with OS benefit, although not confirmed in a Phase 3 study. Arenaviral vectors used in preclinical tumor models could overcome self-tolerance by inducing strong self-antigen specific CD8 T cell responses. In humans, arenaviral vectors encoding HPV16 E7E6 fusion protein (HB-200) induced unprecedented E6E7-specific CD8 T cell levels in patients with recurrent/metastatic HPV16+ cancers. Preliminary clinical activity and favorable safety and tolerability were observed in these heavily pre-treated, checkpoint inhibitor-resistant patients (ref: Fu et al. ASCO 2022; NCT04180215). It is therefore hypothesized that HB-300, a live-attenuated arenaviral vector therapy encoding the self-antigens PAP and PSA, will induce substantially stronger T cell responses in prostate cancer patients than previously tested active immunization approaches. Methods: This is a Phase 1/2 open-label clinical study of HB-300 in ~ 70 patients with advanced mCRPC. A 3+3 Dose Escalation will be followed by a dose-expansion to confirm the recommended Phase 2 dose (RP2D). HB-300 consists of HB-302 (Pichinde virus based) alternating with HB-301 (LCMV based) vectors, administered IV every 3 weeks (Q3W) for 5 doses then Q6W. The program’s entry into the clinic with a mini dose-escalation was supported by the submission of a data master file along with the HB-300 Investigational New Drug application, based on arenavirus vector platform data collected in the HB-200 program. Trial inclusion criteria include male participants age ≥ 18; documented mCRPC (adenocarcinoma without neuroendocrine or small cell features); receipt of at least 1 androgen deprivation therapy and no prior chemotherapy regimens (docetaxel in the castration-sensitive setting is allowed); ≥1 measurable lesion; ECOG PS 0-1. Exclusions are uncontrolled pain or symptoms; active auto-immune disease; immunosuppression; active central nervous system or liver metastasis; and active infection. Phase 1 primary objectives include safety/tolerability and determination of RP2D, secondary objectives include preliminary efficacy, and exploratory assessments include antigen-specific T cell response and circulating tumor cell analysis. Clinical trial# NCT05553639. Clinical trial information: NCT05553639 .